Receptors for the neurotransmitter acetylcholine have been divided into muscarinic and nicotinic. The muscarinic acetylcholine receptors are further divided into tissue subtypes M1 {found primarily in brain cortex}. M2 {found in the heart}, M3 {found in glandular tissue}, and M4 {found in lung tissue}. Recently five different muscarinic acetylcholine receptor proteins have been identified M1, M2, M3, M4, M5. Through use of selective antibodies, the proportion of each of the molecular receptors in each of the tissue type receptors has been determined. A post-mortem study of acetylcholine binding sites in Alzheimer's disease, revealed an increase in M1 density in the striatal area of the brain and a decrease in the M2 density in frontal and temporal cortices and hippocampus. This has led to the theory that Alzheimer's disease is a function of the loss of presynaptic M2 receptor function. The M3 subtype is present in the parotid gland and has been shown to be 93% m3. Thus the m3 receptor may be important in the etiology and treatment of salivary disorders such as Sjogren's Syndrome. R-Quinuclidinyl-R-iodobenzilate (R,R-IQNB,22) has bee labeled with 123I and 125I as an agent for in vitro assays as well as in vivo imaging with single photon emission computer tomography. The absolute configuration at the two chiral centers effects the binding affinity and the pharmacokinetics. The binding affinity of R,R-IQNB for M1 (Ka 8.93 plus/minus 1.36 x 109M-1) is 3 fold higher than its diastereomer, R- quinuclidinyl-S-iodobenzilate (R,S-IQNB), (Ka 2.90 plus/minus 0.45 x 109M-1). However the dissociation rate of R,S-IQNB is 13 times faster from M1 and 21 times faster from m1 than that of R,R-IQNB. The goal of this project is to prepare fluorine containing analogs of IQNB which may be labeled with 18F for imaging by positron emission tomography (PET). We have developed a stereoselective synthesis of chiral benzilic acids based on the use of chiral auxiliary, 8- phenylmenthol. Using this established chiral synthetic method, we have prepared R for S fluoroalkyl benzilic acids which are subsequently coupled for R or S quinuclidinol. The in vitro binding of these fluoroalkyl QNB analogs was evaluated by NovaScreen with a five point binding curve in M1, M2, and M3 assays. R,S-Fluoropropyl QNB and R.S- fluoroethyl QNB display nearly equivalent binding to M1 and M2. However, R.R-fluoroethyl QNB and R,RS-fluoropropyl QNB display nearly 9 fold higher M1 affinity than M2. Of the diasteromeric fluoroethyl QNB analogs, the R.S diastereomer shows 3 fold higher affinity at M1 and 20 fold higher affinity at M2 than the R,R diasteromer. An in vivo study to evaluate subtype selectivity is now in progress.